Molecular Modeling of 4′,5-Disubstituted Biphenyl Acetic Acid Molecules for their Anti-inflammatory Activity through 3D-QSAR, Docking and Molecular Dynamics Simulation

Ananda Sarkar1 and Atish Dipankar Jana2,*

1Department of Physics, Acharya Prafulla Chandra College, Kolkata-700 131, India

2Department of Physics, Behala College, Parnasree, Kolakata-700 060, India

*Corresponding author: E-mail: atish@behalacollege.in; atishdipankarjana@yahoo.in

Abstract

A set of 4′,5-di-substituted 3-biphenyl acetic acid (BPA) and α-methyl derivatives (MBPA) are powerful nonsteroidal anti-inflammatory and analgesic agents. 3D-QSAR analysis through CoMFA and CoMSIA procedures has been carried out for the chosen set of molecules. The CoMSIA analysis reveals that the steric field is more important than the electrostatic field whereas the CoMSIA analysis reveal the importance of hydrophobic field. The docking analysis reveals that besides the hydrogen bonding interaction, π···π and CH···π interactions are also responsible for binding of the molecules in the binding pocket of the COX2 protein (1CX2.pdb). Molecular dynamics (MD) simulation has been performed for the most efficiently bound molecule in the cavity of the COX2 protein. The most stable conformation of the molecule found in molecular dynamics study matches well with its conformation and binding mode obtained from the docking study.

Keywords

COX-inhibition, 3D-QSAR, Molecular docking, Molecular dynamics.

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